03.ecModel_calibration.ipynb

{
 "cells": [
  {
   "attachments": {},
   "cell_type": "markdown",
   "id": "de6a339d",
   "metadata": {},
   "source": [
    "## Import related functions"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 1,
   "id": "748d1c14",
   "metadata": {},
   "outputs": [],
   "source": [
    "import cobra\n",
    "import re \n",
    "import pandas as pd\n",
    "#from script.ECMpy_function import *\n",
    "import sys\n",
    "sys.path.append(r'./script/')\n",
    "from ECMpy_function import *"
   ]
  },
  {
   "attachments": {},
   "cell_type": "markdown",
   "id": "0c1f8ce9",
   "metadata": {},
   "source": [
    "# Input and output files"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "id": "814777ba",
   "metadata": {},
   "outputs": [],
   "source": [
    "#Initial parameters\n",
    "f = 0.406 \n",
    "ptot = 0.56 \n",
    "sigma = 1\n",
    "lowerbound = 0   \n",
    "upperbound = round(ptot * f * sigma, 3) \n",
    "EC_max_file='./data/EC_kcat_max.json'# https://www.brenda-enzymes.org/brenda_download/file_download.php\n",
    "method='AutoPACMEN'#DLKcat\n",
    "use_substrate='EX_glc__D_e'\n",
    "concentration=10\n",
    "obj='BIOMASS_Ec_iML1515_core_75p37M'# CG_biomass_cgl_ATCC13032 EX_lys_L_e\n",
    "\n",
    "#Originl ecmodel and result file\n",
    "ecModel_file=\"./model/iML1515_irr_enz_constraint.json\"\n",
    "fluxes_infile_ori = './analysis/ECMpy_solution_BIOMASS_Ec_iML1515_core_75p37M_pfba.csv'\n",
    "reaction_kcat_MW_file = \"./analysis/get_kcat_mw_by_%s/reaction_kcat_MW.csv\"%method\n",
    "need_change_reaction_list=[]\n",
    "changed_reaction_list=[]\n",
    "round_num=1\n",
    "reaction_kcat_mw = pd.read_csv(reaction_kcat_MW_file, index_col=0)\n",
    "\n",
    "#ecmodel and result file\n",
    "json_output_file = './model/iML1515_irr_enz_constraint_adj.json'\n",
    "reaction_kcat_MW_outfile = './analysis/get_kcat_mw_by_%s/reaction_change_by_enzuse.csv'%method"
   ]
  },
  {
   "attachments": {},
   "cell_type": "markdown",
   "id": "b7f3d628",
   "metadata": {},
   "source": [
    "# Calibration kcat according Enzyme usage "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "id": "21730d4f",
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Need changing reaction: \n",
      "PRFGS\n",
      "Changed reaction: \n",
      "['PRFGS']\n",
      "Calibration round 1 : 0.23173512444593233\n",
      "Need changing reaction: \n",
      "KARA1_reverse\n",
      "Changed reaction: \n",
      "['PRFGS']\n",
      "Calibration round 2 : 0.23173512444593233\n",
      "Need changing reaction: \n",
      "FBA_num1\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1']\n",
      "Calibration round 3 : 0.24483790513370257\n",
      "Need changing reaction: \n",
      "PFL_num3\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3']\n",
      "Calibration round 4 : 0.24723409719596082\n",
      "Need changing reaction: \n",
      "3OAS121\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121']\n",
      "Calibration round 5 : 0.26291740157273025\n",
      "Need changing reaction: \n",
      "3OAS161\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161']\n",
      "Calibration round 6 : 0.2806003508042417\n",
      "Need changing reaction: \n",
      "3OAS141\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141']\n",
      "Calibration round 7 : 0.29935260943266906\n",
      "Need changing reaction: \n",
      "GLUDy_reverse\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141']\n",
      "Calibration round 8 : 0.29935260943266906\n",
      "Need changing reaction: \n",
      "PSERT\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT']\n",
      "Calibration round 9 : 0.3019931955364434\n",
      "Need changing reaction: \n",
      "PAPSR2_num2\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2']\n",
      "Calibration round 10 : 0.3077850507857091\n",
      "Need changing reaction: \n",
      "3OAR60\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60']\n",
      "Calibration round 11 : 0.3137641168450432\n",
      "Need changing reaction: \n",
      "3OAR80\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80']\n",
      "Calibration round 12 : 0.3199800849722744\n",
      "Need changing reaction: \n",
      "3OAR100\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100']\n",
      "Calibration round 13 : 0.3264473195104685\n",
      "Need changing reaction: \n",
      "3OAR40\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40']\n",
      "Calibration round 14 : 0.3331813808664081\n",
      "Need changing reaction: \n",
      "PGCD\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD']\n",
      "Calibration round 15 : 0.34013803712390456\n",
      "Need changing reaction: \n",
      "PFK_num2\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2']\n",
      "Calibration round 16 : 0.3427260533654994\n",
      "Need changing reaction: \n",
      "PGM_reverse_num2\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2']\n",
      "Calibration round 17 : 0.3427260533654994\n",
      "Need changing reaction: \n",
      "PSP_L\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L']\n",
      "Calibration round 18 : 0.34773323581020205\n",
      "Need changing reaction: \n",
      "ACCOAC\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC']\n",
      "Calibration round 19 : 0.3510571116510257\n",
      "Need changing reaction: \n",
      "PTAr_num2\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2']\n",
      "Calibration round 20 : 0.3578952500160452\n",
      "Need changing reaction: \n",
      "3OAR120\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120']\n",
      "Calibration round 21 : 0.36237199885300264\n",
      "Need changing reaction: \n",
      "3OAR140\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140']\n",
      "Calibration round 22 : 0.3669621615609515\n",
      "Need changing reaction: \n",
      "HSDy_reverse_num1\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140']\n",
      "Calibration round 23 : 0.3669621615609515\n",
      "Need changing reaction: \n",
      "3OAR161\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161']\n",
      "Calibration round 24 : 0.370397422352087\n",
      "Need changing reaction: \n",
      "3OAR121\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121']\n",
      "Calibration round 25 : 0.3738976082790336\n",
      "Need changing reaction: \n",
      "3OAR141\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141']\n",
      "Calibration round 26 : 0.379441609584257\n",
      "Need changing reaction: \n",
      "ADSS\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS']\n",
      "Calibration round 27 : 0.3827948676142595\n",
      "Need changing reaction: \n",
      "3OAR160\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160']\n",
      "Calibration round 28 : 0.38391758177386637\n",
      "Need changing reaction: \n",
      "ACONTa_num1\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1']\n",
      "Calibration round 29 : 0.3866375337831847\n",
      "Need changing reaction: \n",
      "IPPS\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS']\n",
      "Calibration round 30 : 0.3892744540703348\n",
      "Need changing reaction: \n",
      "SADT2\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2']\n",
      "Calibration round 31 : 0.39191029957143503\n",
      "Need changing reaction: \n",
      "GAPD\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2']\n",
      "Calibration round 32 : 0.39191029957143503\n",
      "Need changing reaction: \n",
      "GLNS\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS']\n",
      "Calibration round 33 : 0.39392994176634\n",
      "Need changing reaction: \n",
      "ASNS2_num1\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1']\n",
      "Calibration round 34 : 0.3953059242452846\n",
      "Need changing reaction: \n",
      "IPPMIa_reverse\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1']\n",
      "Calibration round 35 : 0.3953059242452846\n",
      "Need changing reaction: \n",
      "IPPMIb_reverse\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1']\n",
      "Calibration round 36 : 0.3953059242452846\n",
      "Need changing reaction: \n",
      "ACOTA_reverse_num2\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1']\n",
      "Calibration round 37 : 0.3953059242452846\n",
      "Need changing reaction: \n",
      "AICART\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1', 'AICART']\n",
      "Calibration round 38 : 0.39574674998410425\n",
      "Need changing reaction: \n",
      "TPI\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1', 'AICART', 'TPI']\n",
      "Calibration round 39 : 0.39619632518648024\n",
      "Need changing reaction: \n",
      "THD2pp\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1', 'AICART', 'TPI', 'THD2pp']\n",
      "Calibration round 40 : 0.3965822171406823\n",
      "Need changing reaction: \n",
      "IMPC_reverse\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1', 'AICART', 'TPI', 'THD2pp']\n",
      "Calibration round 41 : 0.3965822171406823\n",
      "Need changing reaction: \n",
      "PAPPT3\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1', 'AICART', 'TPI', 'THD2pp', 'PAPPT3']\n",
      "Calibration round 42 : 0.3975058418569194\n",
      "Need changing reaction: \n",
      "AIRC2\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1', 'AICART', 'TPI', 'THD2pp', 'PAPPT3', 'AIRC2']\n",
      "Calibration round 43 : 0.39820705457384425\n",
      "Need changing reaction: \n",
      "ASPK_num3\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1', 'AICART', 'TPI', 'THD2pp', 'PAPPT3', 'AIRC2', 'ASPK_num3']\n",
      "Calibration round 44 : 0.39890635782609746\n",
      "Need changing reaction: \n",
      "THRS\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1', 'AICART', 'TPI', 'THD2pp', 'PAPPT3', 'AIRC2', 'ASPK_num3', 'THRS']\n",
      "Calibration round 45 : 0.399605175392766\n",
      "Need changing reaction: \n",
      "AIRC3_reverse\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1', 'AICART', 'TPI', 'THD2pp', 'PAPPT3', 'AIRC2', 'ASPK_num3', 'THRS']\n",
      "Calibration round 46 : 0.399605175392766\n",
      "Need changing reaction: \n",
      "CS\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1', 'AICART', 'TPI', 'THD2pp', 'PAPPT3', 'AIRC2', 'ASPK_num3', 'THRS', 'CS']\n",
      "Calibration round 47 : 0.4001983560070541\n",
      "Need changing reaction: \n",
      "IMPD\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1', 'AICART', 'TPI', 'THD2pp', 'PAPPT3', 'AIRC2', 'ASPK_num3', 'THRS', 'CS', 'IMPD']\n",
      "Calibration round 48 : 0.4007962534772659\n",
      "Need changing reaction: \n",
      "ANS\n",
      "Changed reaction: \n",
      "['PRFGS', 'FBA_num1', 'PFL_num3', '3OAS121', '3OAS161', '3OAS141', 'PSERT', 'PAPSR2_num2', '3OAR60', '3OAR80', '3OAR100', '3OAR40', 'PGCD', 'PFK_num2', 'PSP_L', 'ACCOAC', 'PTAr_num2', '3OAR120', '3OAR140', '3OAR161', '3OAR121', '3OAR141', 'ADSS', '3OAR160', 'ACONTa_num1', 'IPPS', 'SADT2', 'GLNS', 'ASNS2_num1', 'AICART', 'TPI', 'THD2pp', 'PAPPT3', 'AIRC2', 'ASPK_num3', 'THRS', 'CS', 'IMPD', 'ANS']\n",
      "Calibration round 49 : 0.40133927002029507\n"
     ]
    }
   ],
   "source": [
    "#Calibration\n",
    "enz_model_obj=0\n",
    "while (enz_model_obj<0.66 and round_num<50):#maxium growth rate\n",
    "    [enz_model,reaction_kcat_mw,need_change_reaction_list, changed_reaction_list]=change_enz_model_by_enz_usage(ecModel_file,fluxes_infile_ori,EC_max_file,\\\n",
    "                                                    reaction_kcat_mw,need_change_reaction_list,changed_reaction_list,f, \\\n",
    "                                                    ptot, sigma, lowerbound, upperbound, json_output_file)\n",
    "    enz_model.objective=obj\n",
    "    #change original substrate in model\n",
    "    [ori_obj_id,ori_substrate_id_list,ori_sub_concentration,ori_ATPM]=get_model_substrate_obj(enz_model)\n",
    "    for eachsubid in ori_substrate_id_list:\n",
    "        if re.search('_reverse',eachsubid):\n",
    "            r_id_new=eachsubid.split('_reverse')[0]\n",
    "            enz_model.reactions.get_by_id(eachsubid).bounds = (0, 0) \n",
    "            enz_model.reactions.get_by_id(r_id_new).bounds = (0, 0)  \n",
    "        else:\n",
    "            r_id_new=eachsubid+'_reverse'\n",
    "            enz_model.reactions.get_by_id(eachsubid).bounds = (0, 0) \n",
    "            enz_model.reactions.get_by_id(r_id_new).bounds = (0, 0) \n",
    "            \n",
    "    enz_model.reactions.get_by_id(use_substrate).bounds = (-concentration, 0)\n",
    "    enz_model.reactions.get_by_id(use_substrate+'_reverse').bounds = (0, 0)\n",
    "\n",
    "    enz_model_obj=enz_model.slim_optimize()\n",
    "    print('Calibration round %s : '%round_num+str(enz_model_obj))\n",
    "    round_num=round_num+1\n",
    "    \n",
    "reaction_kcat_mw.to_csv(reaction_kcat_MW_outfile)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "461cd945",
   "metadata": {},
   "outputs": [],
   "source": []
  }
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